We are investigating the methylation of the E-amino groups of lysine in the arginine-rich histones from various tissues of the rat, particularly brain. Only the H3 and H4 histones contain significant amounts of methylated amino acid residues. The product of methylation of H4 is predominantly dimethyllysine with trace quantities of monomethyllysine present in rapidly proliferating tissue. The total amount of dimethyllysine in H4 is 1.0 mole/mole polypeptide. The products of methylation of H3 are mono-, di- and trimethyllysine in a mole ration of 0.55:1.0:0.35. Both in vivo and in vitro experiments indicate the methylation of H3 and H4 occurs after the histones are bound to DNA. In vitro studies indicate that methylation proceeds stepwise, hence mono-to dimethyllysine in H4 and mono- to di-trimethyllysine in H3. The enzyme(s) catalyzing these reactions are firmly bound to chromatin. The enzymes can be solubilized by sequential elution with high salt concentrations. When assayed against soluble total histone all subfractions are methylated while only histones H3 and H4 undergo methylation when the histones are bound to DNA. Purification procedures and properties of the histone methyltransferases are presntly under investigation. BIBLIOGRAPHIC REFERENCES: Walker, R.D. and Duerre, J.A. S-Adenosylhomocysteine Metabolism in Various Species. Can. J. Biochem. 53: 312, 1975. Duerre, J.A. and Chakrabarty, S. Distribution of Methylated Basic Amino Acid Residues in Histones from Various Organs of the Rat. Fed. Proc., 34, 2213, 1975.